2024
Genetic ancestry, proportion of African ancestry, and apolipoprotein L1 risk variants in kidney recipients
Zhang Z, Sun Z, Heeger P, Menon M. Genetic ancestry, proportion of African ancestry, and apolipoprotein L1 risk variants in kidney recipients. American Journal Of Transplantation 2024, 24: 1710-1712. PMID: 38734416, DOI: 10.1016/j.ajt.2024.05.004.Peer-Reviewed Original ResearchRationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis
Barsotti G, Luciano R, Kumar A, Meliambro K, Kakade V, Tokita J, Naik A, Fu J, Peck E, Pell J, Reghuvaran A, Tanvir E, Patel P, Zhang W, Li F, Moeckel G, Perincheri S, Cantley L, Moledina D, Wilson F, He J, Menon M. Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis. Kidney International Reports 2024, 9: 1354-1368. PMID: 38707807, PMCID: PMC11068976, DOI: 10.1016/j.ekir.2024.02.006.Peer-Reviewed Original ResearchMinimal change diseaseRandomized controlled trialsSafety of metforminDouble-blindPodocyte injuryAdjunctive therapyPlacebo-controlled randomized controlled trialsPhase III studyPhase II trialPrimary glomerular diseaseFocal segmental glomerulosclerosisEffect of metforminPhase IIPlacebo-controlledPreclinical dataNovel urineChange diseaseTissue markersRandomized trialsSegmental glomerulosclerosisGlomerular diseaseMechanistic biomarkersObservational studyFSGSInexpensive agentAdvancing mouse models for transplantation research
Cravedi P, Riella L, Ford M, Valujskikh A, Menon M, Kirk A, Alegre M, Alessandrini A, Feng S, Kehn P, Najafian N, Hancock W, Heeger P, Maltzman J, Mannon R, Nadig S, Odim J, Turnquist H, Shaw J, West L, Luo X, Chong A, Bromberg J, group A. Advancing mouse models for transplantation research. American Journal Of Transplantation 2024, 24: 1362-1368. PMID: 38219866, PMCID: PMC11239793, DOI: 10.1016/j.ajt.2024.01.006.Peer-Reviewed Original ResearchMouse modelMechanisms of transplant rejectionTranslation to clinical trialsFood and Drug Administration-approved drugsMouse transplantation modelEffective clinical therapiesAdvanced mouse modelsTranslation of experimental findingsClinical outcomesTransplantation modelTransplant rejectionClinical trialsMouse studiesClinical therapyTransplantationClinical researchPhysician-scientistsGenetic variabilityTherapyStatistical power analysis
2023
A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization
Yi Z, Xi C, Menon M, Cravedi P, Tedla F, Soto A, Sun Z, Liu K, Zhang J, Wei C, Chen M, Wang W, Veremis B, Garcia-Barros M, Kumar A, Haakinson D, Brody R, Azeloglu E, Gallon L, O'Connell P, Naesens M, Shapiro R, Colvin R, Ward S, Salem F, Zhang W. A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization. Kidney International 2023, 105: 281-292. PMID: 37923131, PMCID: PMC10892475, DOI: 10.1016/j.kint.2023.09.031.Peer-Reviewed Original ResearchArterial intimal fibrosisGraft lossOrgan utilizationIntimal fibrosisSclerotic glomeruliLarge-scale retrospective studyGlomerular filtration rateDeceased donor kidneysPathologist scoresTransplant outcomesBiopsy findingsSurvival prediction modelWedge biopsyRisk stratificationRetrospective studyFiltration ratePathological assessmentDonor biopsiesNeedle biopsySimilar survivalHistological scoringUnnecessary organsDiscovery setKidneyLesion scoresMultiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival
Sun Z, Zhang Z, Banu K, Gibson I, Colvin R, Yi Z, Zhang W, De Kumar B, Reghuvaran A, Pell J, Manes T, Djamali A, Gallon L, O'Connell P, He J, Pober J, Heeger P, Menon M. Multiscale genetic architecture of donor-recipient differences reveals intronic LIMS1 mismatches associated with kidney transplant survival. Journal Of Clinical Investigation 2023, 133: e170420. PMID: 37676733, PMCID: PMC10617779, DOI: 10.1172/jci170420.Peer-Reviewed Original ResearchConceptsDeath-censored graft lossHuman leukocyte antigenExpression quantitative trait lociT cellsTGF-β1TGF-β1/Smad pathwayDonor-recipient differencesKidney allograft lossChronic allograft rejectionKidney transplant survivalDonor-recipient mismatchActive TGF-β1Allograft lossGraft lossAllograft rejectionTransplant cohortPeripheral bloodLeukocyte antigenClinical trialsImmune cellsHaplotype mismatchGenome-wide scaleTransplant survivalQuantitative trait lociSingle nucleotide polymorphism dataNonpodocyte Roles of APOL1 Variants: An Evolving Paradigm
Pell J, Nagata S, Menon M. Nonpodocyte Roles of APOL1 Variants: An Evolving Paradigm. Kidney360 2023, 4: e1325-e1331. PMID: 37461136, PMCID: PMC10550003, DOI: 10.34067/kid.0000000000000216.Peer-Reviewed Original ResearchConceptsApolipoprotein L1Progressive renal failureAPOL1 risk variantsImmune response genesParadigm of diseasesMechanisms of diseaseRenal failureKidney diseaseBody of evidenceImmune cellsClinical dataRecent African ancestryRisk genotypesAPOL1 variantsDiseaseEndothelial cellsPutative signaling pathwaysGenetic factorsSeminal dataPhenotype progressionCausal rolePodocytesRisk variantsSignaling pathwaysEvolving ParadigmHCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy
Chen M, Menon M, Wang W, Fu J, Yi Z, Sun Z, Liu J, Li Z, Mou L, Banu K, Lee S, Dai Y, Anandakrishnan N, Azeloglu E, Lee K, Zhang W, Das B, He J, Wei C. HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy. Nature Communications 2023, 14: 4297. PMID: 37463911, PMCID: PMC10354075, DOI: 10.1038/s41467-023-40086-3.Peer-Reviewed Original ResearchConceptsChronic kidney diseasePro-inflammatory polarizationBone marrow-derived macrophagesRenal inflammationKidney fibrosisMacrophage activationHematopoietic cell kinaseMacrophage pro-inflammatory activityProgressive chronic kidney diseaseIschemia-reperfusion injury modelUnilateral ureteral obstruction kidneysChronic allograft injuryReperfusion injury modelPro-inflammatory activityPro-inflammatory macrophagesHck inhibitorsMarrow-derived macrophagesSuppression of autophagyAllograft injuryUUO miceRenal fibrosisKidney diseaseDiseased kidneysMacrophage numbersInjury modelComparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli
Reghuvaran A, Lin Q, Basgen J, Banu K, Shi H, Vashist A, Pell J, Perinchery S, He J, Moledina D, Wilson F, Menon M. Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli. Physiological Reports 2023, 11: e15688. PMID: 37423891, PMCID: PMC10329935, DOI: 10.14814/phy2.15688.Peer-Reviewed Original ResearchWCN23-0470 BAC-transgenic mice show a novel T-cell intrinsic role for FSGS-associated APOL1 risk-variants in T-cell activation
Pell J, Reghuvaran A, Nagata S, Banu K, He J, Craft J, Shi H, Chernova I, Ishibe S, Menon M. WCN23-0470 BAC-transgenic mice show a novel T-cell intrinsic role for FSGS-associated APOL1 risk-variants in T-cell activation. Kidney International Reports 2023, 8: s392-s393. DOI: 10.1016/j.ekir.2023.02.882.Peer-Reviewed Original ResearchAllograft tissue under the microscope: only the beginning
Virmani S, Rao A, Menon M. Allograft tissue under the microscope: only the beginning. Current Opinion In Organ Transplantation 2023, 28: 126-132. PMID: 36787238, PMCID: PMC10214011, DOI: 10.1097/mot.0000000000001052.Peer-Reviewed Original ResearchConceptsAllograft tissueArtificial intelligenceBanff schemaMachine learningDigital pathologyKidney allograft biopsiesApplication of AINovel molecular diagnosticsAllograft healthAllograft histologyAllograft biopsiesPathologic diagnosisImmunological activationTissue injuryHistopathological analysisClinical careTissue pathologyML algorithmsClinical useOrdinal outputsNovel modalityVivo microscopyPathologyBiopsyTissue
2022
Walking the Line Between Antidonor and Antiviral Immunity: A Potential Role for Belatacept
Gunasekaran D, Pell J, Menon M. Walking the Line Between Antidonor and Antiviral Immunity: A Potential Role for Belatacept. Kidney International Reports 2022, 8: 1-3. PMID: 36644356, PMCID: PMC9832058, DOI: 10.1016/j.ekir.2022.11.005.Commentaries, Editorials and LettersBlood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity
Sun Z, Zhang Z, Banu K, Al Azzi Y, Reghuvaran A, Fredericks S, Planoutene M, Hartzell S, Kim Y, Pell J, Tietjen G, Asch W, Kulkarni S, Formica R, Rana M, Maltzman JS, Zhang W, Akalin E, Heeger PS, Cravedi P, Menon MC. Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity. Journal Of The American Society Of Nephrology 2022, 33: 2108-2122. PMID: 36041788, PMCID: PMC9678030, DOI: 10.1681/asn.2022010125.Peer-Reviewed Original ResearchConceptsKidney transplant recipientsImmune activation pathwaysImmunosuppressant useKTR cohortAcute illnessBlood transcriptomeAcute casesT cellsCOVID-19Most kidney transplant recipientsPost-acute COVID-19Adaptive immune system activationManagement of immunosuppressionReinstitution of immunosuppressionAcute COVID-19Serum inflammatory cytokinesCOVID-19 severity scoreCOVID-19 infectionImmune system activationUpregulation of neutrophilActivation pathwayTransplant recipientsChart reviewImmune signaturesLymphocyte countA Novel Role of APOL1 Risk-Alleles in T-Cell Activation and Focal Segmental Glomerulosclerosis
Pell J, Reghuvaran A, Nagata S, Banu K, Shi H, Chernova I, Ishibe S, Menon M. A Novel Role of APOL1 Risk-Alleles in T-Cell Activation and Focal Segmental Glomerulosclerosis. Journal Of The American Society Of Nephrology 2022, 33: 410-411. DOI: 10.1681/asn.20223311s1410d.Peer-Reviewed Original ResearchInfliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial
Hricik D, Armstrong B, Alhamad T, Brennan D, Bromberg J, Bunnapradist S, Chandran S, Fairchild R, Foley D, Formica R, Gibson I, Kesler K, Kim SJ, Mannon R, Menon M, Newell K, Nickerson P, Odim J, Poggio E, Sung R, Shapiro R, Tinckam K, Vincenti F, Heeger P. Infliximab Induction Lacks Efficacy and Increases BK Virus Infection in Deceased Donor Kidney Transplant Recipients: Results of the CTOT-19 Trial. Journal Of The American Society Of Nephrology 2022, 34: 145-159. PMID: 36195441, PMCID: PMC10101585, DOI: 10.1681/asn.2022040454.Peer-Reviewed Original ResearchConceptsBiopsy-proven acute rejectionBK virus infectionIntravenous infliximabPrimary end pointTransplant recipientsKidney transplantVirus infectionDe novo donor-specific antibodiesDeceased donor kidney transplant recipientsRabbit anti-thymocyte globulin (rATG) inductionAnti-thymocyte globulin inductionCLINICAL TRIAL REGISTRY NAMEDonor kidney transplant recipientsNovo donor-specific antibodiesEnd pointPhase 2 clinical trialIFX induction therapyTRIAL REGISTRY NAMEDelayed graft functionDonor-specific antibodiesKidney transplant recipientsDeceased donor kidneysTNF-α productionPrimary transplant recipientsAcute rejectionCellular recovery after prolonged warm ischaemia of the whole body
Andrijevic D, Vrselja Z, Lysyy T, Zhang S, Skarica M, Spajic A, Dellal D, Thorn SL, Duckrow RB, Ma S, Duy PQ, Isiktas AU, Liang D, Li M, Kim SK, Daniele SG, Banu K, Perincheri S, Menon MC, Huttner A, Sheth KN, Gobeske KT, Tietjen GT, Zaveri HP, Latham SR, Sinusas AJ, Sestan N. Cellular recovery after prolonged warm ischaemia of the whole body. Nature 2022, 608: 405-412. PMID: 35922506, PMCID: PMC9518831, DOI: 10.1038/s41586-022-05016-1.Peer-Reviewed Original ResearchConceptsSingle-nucleus transcriptomic analysesSpecific gene expression patternsCellular recoveryGene expression patternsCellular processesMammalian cellsTranscriptomic analysisLarge mammalsExpression patternsCellular repair processesCell deathComprehensive resourceUnderappreciated potentialPhysiological challengesTissue integrityRepair processSpecific changesPorcine brainMammalsOrgansMultiple organsDonor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms
Jethwani P, Rao A, Bow L, Menon MC. Donor–Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms. Frontiers In Immunology 2022, 13: 822353. PMID: 35432337, PMCID: PMC9012490, DOI: 10.3389/fimmu.2022.822353.Peer-Reviewed Original ResearchConceptsAllograft outcomesImportant recent dataRenal allograft outcomeAcute allograft rejectionKidney allograft outcomesDonor-recipient mismatchRecipient's immune systemNatural history studiesNon-HLA lociMajority of casesOrgan allocation processPolymorphic HLA genesAcute rejectionAllograft longevityAllograft lossMaintenance immunosuppressionTransplant outcomesAllograft rejectionImmune mechanismsPatient deathRecipient pairsDonor organsHLA variantsImmune systemOvert evidence
2021
Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes
Zhang Z, Sun Z, Fu J, Lin Q, Banu K, Chauhan K, Planoutene M, Wei C, Salem F, Yi Z, Liu R, Cravedi P, Cheng H, Hao K, O’Connell P, Ishibe S, Zhang W, Coca SG, Gibson IW, Colvin RB, He J, Heeger PS, Murphy B, Menon MC. Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes. Journal Of Clinical Investigation 2021, 131 PMID: 34499625, PMCID: PMC8592534, DOI: 10.1172/jci146643.Peer-Reviewed Original ResearchConceptsDeath-censored allograft lossAPOL1 risk allelesRisk allelesTransplant outcomesDeath-censored renal allograft survivalRenal allograft survivalChronic allograft rejectionKidney transplant waitlistKidney transplant cohortRisk allele carriersAllograft lossAllograft survivalGraft lossRejection episodesTransplant cohortAllograft rejectionDonor kidneysNative kidneysNK cellsImmunomodulatory roleTransplant waitlistAPOL1 genotypeClinical trialsHealthy controlsHispanic recipientsDeep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies
Yi Z, Salem F, Menon MC, Keung K, Xi C, Hultin S, Haroon Al Rasheed MR, Li L, Su F, Sun Z, Wei C, Huang W, Fredericks S, Lin Q, Banu K, Wong G, Rogers NM, Farouk S, Cravedi P, Shingde M, Smith RN, Rosales IA, O'Connell PJ, Colvin RB, Murphy B, Zhang W. Deep learning identified pathological abnormalities predictive of graft loss in kidney transplant biopsies. Kidney International 2021, 101: 288-298. PMID: 34757124, PMCID: PMC10285669, DOI: 10.1016/j.kint.2021.09.028.Peer-Reviewed Original ResearchConceptsGraft lossTransplant biopsiesDamage scoreBanff scoresPathological lesionsOne-year graft lossPost-transplant graft lossGlomerular filtration rate declineIntermediate-risk groupKidney allograft failurePost-transplant biopsiesKidney transplant biopsiesMononuclear leukocyte infiltrationTissue compartmentsMononuclear leukocyte infiltrateProtocol biopsiesAllograft failureTransplant recipientsClinical predictorsTubular atrophyGraft damageRisk stratificationInterstitial fibrosisLeukocyte infiltrationLeukocyte infiltrateAMP-Kinase mediates regulation of glomerular volume and podocyte survival
Banu K, Lin Q, Basgen JM, Planoutene M, Wei C, Reghuvaran AC, Tian X, Shi H, Garzon F, Garzia A, Chun N, Cumpelik A, Santeusanio AD, Zhang W, Das B, Salem F, LI L, Ishibe S, Cantley LG, Kaufman L, Lemley KV, Ni Z, He JC, Murphy B, Menon MC. AMP-Kinase mediates regulation of glomerular volume and podocyte survival. JCI Insight 2021, 6: e150004. PMID: 34473647, PMCID: PMC8525649, DOI: 10.1172/jci.insight.150004.Peer-Reviewed Original ResearchAdenylate KinaseAdolescentAdultAgedAlbuminuriaAnimalsCell SizeCell SurvivalChildChild, PreschoolFemaleGene Knockdown TechniquesGlomerulonephritis, MembranousGlomerulosclerosis, Focal SegmentalHumansHypertrophyInfantKidney GlomerulusMaleMiceMicrofilament ProteinsMiddle AgedNephrectomyNephrosis, LipoidNephrotic SyndromePodocytesProportional Hazards ModelsProto-Oncogene Proteins c-fynYoung AdultROCK-Binding ASD2-Domain of Shroom3 Has a Profibrotic Role
Lin Q, Banu K, Reghuvaran A, Wei C, He J, Murphy B, Menon M. ROCK-Binding ASD2-Domain of Shroom3 Has a Profibrotic Role. Journal Of The American Society Of Nephrology 2021, 32: 754-754. DOI: 10.1681/asn.20213210s1754a.Peer-Reviewed Original Research